1990 Volume 36 Pages 41-49
In shelf freeze-drying of pharmaceuticals, it is one of the important problems to realize "intervial uniformity" and "batch to batch uniformity or consisitency". For one of the themes on the problem, necessity of uniform shelf temperatures (e.g., within ±1℃, both across and between shelves) has been stressed by both manufacturers and users of freeze-dryers, while significant intervial variance in the sublimation rate has been pointed out by several authors, Rowe (1979), Pikal (1985), and Kobayashi (1982), (1988) for the placement of the vials put on a well controled shelf. However, all of previous works on this important problem merely described the phenomena observed in the experiments or the production processes, they did not propose clearly the way to solve the problem. This presentation discusses a method for eliminating the intervial variances in the drying conditions and to shorten drying time. In this study, authors have developed a new model of labo-scale pilot freeze-dryer having temperature controlable chamber wall, and using this system authors have made clear that the higher sublimation rate for vials placed on the shelf edge is due to an additional heat input from the edge of the shelf (Δq_h), mainly by conduction effect through the gas between the shelf surface, and also due to another additional heat input from the wall (Δq_w), mainly by radiation effect. Under the certain geometrical conditions, since these additional heat inputs, one from the shelf (Δq_h) and another from the walls (Δq_w) to each of the edge vials, have almost similar pattern (Δq_h/Δq_w ≒ const. for each vial forming the perimeter of a group of vials), it is possible to cancel the additional heat input from the shelf by maintaining the optimum wall temperature which must be a little lower than the material temperature (t_w < t_m, Δq_w < 0, & Δq_h + Δq_w = 0). In order to realize the wall temperature control successfully in a production scale freeze-dryer, it is necessary to make the wall surface reflectance for thermal radiation lower than that of bright polished stainless steel surface.
